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Drug: Safinamide plus Levodopa vs Placebo plus Levodopa
Reference: Borgohain R, et al, 2014 (Study 016)6
Study Design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study
Study Funding: Newron Pharmaceuticals, Merck Serono
Patients: 669 patients with idiopathic Parkinson disease
(Hoehn and Yahr stage I to IV) stabilized on levodopa for
at least 4 weeks. Patients' disease was marked by a period
of more than 1.5 h/d of "off" time (referring to times of
decreased mobility, whereas "on" time refers to times during which medication therapy controls Parkinson disease
symptoms). Individual diaries of "on" and "off" times had
to be maintained. At baseline, average patient age was 60
years; 71.7% were male; 19.4% were white and 80.6%
Asian; and average duration of Parkinson disease was 8
years. Mean UPDRS part III score was approximately 28,
with no meaningful differences among treatment groups.
Concomitant Parkinson disease medications included
dopamine agonist (approximately 60.8%), entacapone
(approximately 24.4%), anticholinergic (approximately
37.1%), and/or amantadine (approximately 13.9%).
Patients were excluded if they had severe, disabling peakdose or biphasic dyskinesia or unpredictable or wide fluctuations; or evidence of dementia, major psychiatric
illnesses, and/or severe progressive medical illnesses.
Intervention: Patients were randomized 1:1:1 to receive
safinamide 50 mg (n = 223), safinamide 100 mg (n =
224), or placebo (n = 222) once daily with breakfast for
24 weeks. All patients were maintained on their preenrollment dose of levodopa throughout the study; however, the
levodopa dose could be increased or other Parkinson disease medications (except MAO-B inhibitors) added as
rescue therapy.

Results
Primary End Point(s)
** In the ITT population, least squares (LS) mean change
from baseline to week 24 in total daily "on" time with
no to nontroublesome dyskinesia was 1.23 hours with
safinamide 50 mg (LS mean change vs placebo of
0.51 hours [95% CI, 0.07-0.94; P = .0223]), 1.26
hours with safinamide 100 mg (LS mean change vs
placebo of 0.55 hours [95% CI, 0.12-0.99; P = .013]),
and 0.8 hours with placebo.

Secondary End Point(s)
** Average total daily "off" time at week 24 was 3.9
hours with safinamide 50 mg, 3.9 hours with safinamide 100 mg, and 4.6 hours with placebo. The average LS mean difference versus placebo was −0.6
(95% CI, −0.9 to −0.2; P = .0043) for safinamide 50
mg and −0.6 (95% CI, −1 to −0.2; P = .0034) for

Hospital Pharmacy 52(8)
safinamide 100 mg. Average "off" time following the
morning dose of levodopa at week 24 was 3.6 hours
with safinamide 50 mg, 3.5 hours with safinamide 100
mg, and 4.2 hours with placebo. The average change
in "off" time following the levodopa dose from baseline to week 24 was −1.1 with safinamide 50 mg (P =
.0031), −1.2 with safinamide 100 mg (P = .0011), and
−0.6 with placebo.
** Average difference between baseline and week 24
UPDRS part III (motor examination) score was −6.1
with safinamide 50 mg (LS mean change vs placebo of
−1.8 [95% CI, −3.3 to −0.4; P = .0138]), −6.9 with
safinamide 100 mg (LS mean change vs placebo of
−2.6 [95% CI, −4.1 to −1.1; P < .001]), and −4.3 with
placebo. Average change in UPDRS part II (activities
of daily living) score from baseline was only significant
for the 100 mg group (−2.2; P = .006 vs placebo).
** Percentage of patients showing improvement in
CGI-C scores at week 24 was 66.4% in the 50 mg
group (P = .001 vs placebo), 64.3% in the 100 mg
group (P = .0089), and 55.4% in the placebo group.
Average change in CGI-S score from baseline to week
24 was −0.4 with safinamide 50 mg (P = .006 vs placebo), −0.4 with safinamide 100 mg (P = .0448 vs
placebo), and −0.2 with placebo.
** No significant between-group differences were
observed in changes from baseline to week 24 in
Dyskinesia Rating Scale (DRS) scores during "on"
time or in levodopa dose reduction percentages.

End Point(s)
** Average change from baseline in Parkinson Disease
Questionnaire (PDQ-39) subscale score was significant for emotional well-being, communication, and
bodily discomfort in the 100 mg group. The other subscale scores (reflecting mobility, stigma, social support, and cognition) were not statistically different
from placebo score changes.
** No significant differences were observed in mean
change from baseline for HAMD score in both groups.
Comments: The study targeted a patient population with
mid- to late-stage Parkinson disease. The majority of
patients (87%-90%) remained at their preenrolled dose of
levodopa throughout the study. Eighty-nine percent of the
enrolled patients completed the study. More patients in
the placebo group reported increased Parkinson disease
symptoms and depression, while more patients in the
safinamide groups reported increased dyskinesia. Reasons
for discontinuing study drug included nonserious adverse
events (3.9%) and withdrawal of consent (2.7%).
Limitations: This study was not conducted in the United
States; subjects were recruited from India (80.6%),
Romania (15.8%), and Italy (3.6%).



Table of Contents for the Digital Edition of Hospital Pharmacy - September 2017

Pharmacy Transitions of Care and Culture
Bivalirudin Medication Use Evaluation and Cost Savings Initiative
Navigating the New Antimicrobial Stewardship Regulations
Safinamide
Biosimilar Substitution Laws
Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Hazardous Drug Contamination of Drug Preparation Devices and Staff: A Contamination Study Simulating the Use of Chemotherapy Drugs in a Clinical Setting
A Case of Metronidazole Injection Infiltration Without Sequelae
Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists’ Clinical Activities and Team Members’ Satisfaction
Extended Stability of Epinephrine Hydrochloride Injection in Polyvinyl Chloride Bags Stored in Amber Ultraviolet Light–Blocking Bags
Formation of a Citywide Pharmacy Residents’ Collaborative Committee
Hospital Pharmacy - September 2017 - 513
Hospital Pharmacy - September 2017 - 514
Hospital Pharmacy - September 2017 - 515
Hospital Pharmacy - September 2017 - 516
Hospital Pharmacy - September 2017 - 517
Hospital Pharmacy - September 2017 - 518
Hospital Pharmacy - September 2017 - 519
Hospital Pharmacy - September 2017 - Pharmacy Transitions of Care and Culture
Hospital Pharmacy - September 2017 - 521
Hospital Pharmacy - September 2017 - Bivalirudin Medication Use Evaluation and Cost Savings Initiative
Hospital Pharmacy - September 2017 - 523
Hospital Pharmacy - September 2017 - 524
Hospital Pharmacy - September 2017 - 525
Hospital Pharmacy - September 2017 - 526
Hospital Pharmacy - September 2017 - Navigating the New Antimicrobial Stewardship Regulations
Hospital Pharmacy - September 2017 - 528
Hospital Pharmacy - September 2017 - 529
Hospital Pharmacy - September 2017 - 530
Hospital Pharmacy - September 2017 - 531
Hospital Pharmacy - September 2017 - Safinamide
Hospital Pharmacy - September 2017 - 533
Hospital Pharmacy - September 2017 - 534
Hospital Pharmacy - September 2017 - 535
Hospital Pharmacy - September 2017 - 536
Hospital Pharmacy - September 2017 - 537
Hospital Pharmacy - September 2017 - 538
Hospital Pharmacy - September 2017 - 539
Hospital Pharmacy - September 2017 - 540
Hospital Pharmacy - September 2017 - 541
Hospital Pharmacy - September 2017 - 542
Hospital Pharmacy - September 2017 - 543
Hospital Pharmacy - September 2017 - Biosimilar Substitution Laws
Hospital Pharmacy - September 2017 - 545
Hospital Pharmacy - September 2017 - Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Hospital Pharmacy - September 2017 - 547
Hospital Pharmacy - September 2017 - 548
Hospital Pharmacy - September 2017 - 549
Hospital Pharmacy - September 2017 - 550
Hospital Pharmacy - September 2017 - Hazardous Drug Contamination of Drug Preparation Devices and Staff: A Contamination Study Simulating the Use of Chemotherapy Drugs in a Clinical Setting
Hospital Pharmacy - September 2017 - 552
Hospital Pharmacy - September 2017 - 553
Hospital Pharmacy - September 2017 - 554
Hospital Pharmacy - September 2017 - 555
Hospital Pharmacy - September 2017 - 556
Hospital Pharmacy - September 2017 - 557
Hospital Pharmacy - September 2017 - 558
Hospital Pharmacy - September 2017 - A Case of Metronidazole Injection Infiltration Without Sequelae
Hospital Pharmacy - September 2017 - 560
Hospital Pharmacy - September 2017 - 561
Hospital Pharmacy - September 2017 - 562
Hospital Pharmacy - September 2017 - 563
Hospital Pharmacy - September 2017 - Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists’ Clinical Activities and Team Members’ Satisfaction
Hospital Pharmacy - September 2017 - 565
Hospital Pharmacy - September 2017 - 566
Hospital Pharmacy - September 2017 - 567
Hospital Pharmacy - September 2017 - 568
Hospital Pharmacy - September 2017 - 569
Hospital Pharmacy - September 2017 - Extended Stability of Epinephrine Hydrochloride Injection in Polyvinyl Chloride Bags Stored in Amber Ultraviolet Light–Blocking Bags
Hospital Pharmacy - September 2017 - 571
Hospital Pharmacy - September 2017 - 572
Hospital Pharmacy - September 2017 - 573
Hospital Pharmacy - September 2017 - Formation of a Citywide Pharmacy Residents’ Collaborative Committee
Hospital Pharmacy - September 2017 - 575
Hospital Pharmacy - September 2017 - 576
Hospital Pharmacy - September 2017 - 577
Hospital Pharmacy - September 2017 - 578
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